The TAM receptors (tyro 3, axl, mer) have emerged in recent years as master regulators of macrophage and dendritic cell activation and phagocytosis. Absence of one or more of these tyrosine kinases results in inflammation and autoimmunity. The TAM receptors are attractive targets for in vivo therapy with monoclonal antibodies or recombinant ligands. Stimulation through these molecules promotes a shift of cytokine production away from M1 inflammatory macrophages to M2 non- inflammatory, reparative cells, and decreases dendritic cell type I interferon secretion and activation. Such a modulation of macrophage and DC function may be desirable for inflammatory arthritis and diverse autoimmune conditions. In this proposal, we wish to explore the potential of antibodies to mer to modulate DC function in vitro, and to administer these antibodies in vivo to animals to assess their effects on the immune response. Through these preclinical studies, we expect to learn more about the biology of the receptors and to provide data to guide a parallel therapeutic approach in humans.